Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings.

STUDY OBJECTIVE: To compare the absolute bioavailability of phenytoin (PHT) sodium solution and PHT acid suspension in healthy volunteers receiving continuously infused enteral feedings. DESIGN: Randomized, open-label, single-dose, three-period crossover study. SETTING: University clinical research center. SUBJECTS: Ten healthy volunteers age 23-43 years. INTERVENTIONS: The three phases of the study were separated by at least 7 days. During phase A, subjects received PHT sodium 435 mg intravenously over 30 minutes. During phases B and C, subjects had a nasogastric feeding tube placed through which PHT acid suspension 400 mg and PHT sodium solution 435 mg were administered, respectively. For phases B and C, continuous enteral feedings were given by feeding tube for 14 hours before and after the PHT dose. Blood samples were collected over 72 hours after each PHT dose, and the serum was analyzed for PHT. MEASUREMENTS AND MAIN RESULTS: The rate and extent of PHT absorption and PHT pharmacokinetics were determined using an empirical quadratic function of time method. Bioavailability, rate of absorption, maximum concentration (Cmax), and time to maximum concentration (Tmax) were compared for the two enteral doses by paired Student's t test. There were no significant differences in bioavailability for PHT acid suspension and PHT sodium solution (0.88 +/- 0.15 vs 0.91 +/- 0.7, p=0.57, 90% CI -0.14-0.071). The Cmax was greater (7.4 +/- 0.9 mg/L vs 5.5 +/- 1.7 mg/L, p=0.019) and Tmax was less (2.5 +/- 3.8 vs.14.8 +/- 11.2 hrs, p=0.004) for the sodium solution. The time to 50% fractional absorption (0.33 +/- 0.08 vs 3.2 +/- 2.4 hrs, p=0.004) and 90% fractional absorption (7.9 +/- 6.2 vs 22.3 +/- 17.2 hrs, p=0.021) was also significantly shorter for the sodium solution. CONCLUSION: The absolute bioavailability of the two dosage forms of PHT administered with concomitant enteral feedings were not significantly different, however, the absorption patterns were significantly different, with the sodium solution being more rapidly absorbed.

The role of calcium-channel antagonists in solid organ transplantation.

Calcium-channel antagonists play a role not only in the management of cardiovascular disease, but they may also play a role in solid organ transplantation. Part of the success of solid organ transplantation over the last several years has been the development of potent immunosuppressive agents such as cyclosporine A and tacrolimus. The calcium-channel antagonists have been shown to decrease cyclosporine A-induced nephrotoxicity by blocking the vasoconstrictive effects of endothelin and thromboxane A2 on the afferent arteriole induced by this agent. The role of calcium antagonists in avoiding tacrolimus-induced nephrotoxicity has not been studied to date. Calcium antagonists have been shown to have an immune-modulating effect as well, via inhibition of calcium-mediated lymphocyte proliferation. This immune-modulating effect has resulted in a decreased incidence of acute rejection in those patients receiving concomitant cyclosporine and calcium antagonists. A third role for calcium antagonists in organ transplantation has been as an additive to organ preservation solutions to avoid calcium-mediated ischemic damage. Despite several successful investigations demonstrating a role for calcium antagonists in solid organ transplantation, widespread acceptance of such a role awaits larger randomized clinical trials.

Documenting pharmacists' interventions on a hospital's mainframe computer system.

The development and implementation of a code that enables pharmacists to document their clinical interventions in the hospital's computerized patient records is described. To allow data to be entered in patient records from terminals throughout the hospital that are linked to the mainframe computer, a code was developed to summarize each pharmacist recommendation. The coded information is added to the computer entry for the specific drug requiring intervention. A computer program was developed inhouse for generating daily reports of the pharmacist interventions. During an initial 25-day study period, 300 interventions were documented; house staff physicians accepted the pharmacists' recommendations in 257 (85.7%) of these interventions. An additional 17 (6%) of the interventions resulted from physicians' requests for pharmacists' recommendations. In addition to review of all pharmacist clinical interventions, this system allows review of a specific target drug to determine compliance with institutional drug-use guidelines. Through use of the computer program developed at this hospital, information that documents pharmacists' clinical services can be entered directly into patients' records on the hospital's mainframe computer system and retrieved as useful reports.

Reducing cocaine solution use by promoting the use of a lidocaine-phenylephrine solution.

A program to reduce the use of cocaine solution in a university teaching hospital by promoting the use of a lidocaine-phenylephrine solution is described. To reduce the use of cocaine solution, pharmacists promoted the use of a mixture of lidocaine 3% and phenylephrine 0.25% in place of cocaine solution for nasotracheal intubation procedures. Because initial clinical use of the lidocaine-phenylephrine solution by the anesthesia service was successful, the pharmacy department began in December 1986 to actively promote use of the solution to the bronchoscopy service, the emergency service, and select inpatient nursing units. Educational measures included an article in the pharmacy and therapeutics newsletter detailing the safety and efficacy of the solution, pharmacist description of the program to physicians and nurses, and designation of the solution as a free floor stock item on nursing units. By 1988, total cocaine solution use had decreased by 66% from the 1984 average of 145.7 doses per month to an average of 50.0 doses per month; overall use of topical anesthetics remained constant. The nursing staff supported the use of the lidocaine-phenylephrine solution because it eliminated the extensive record keeping necessary for the cocaine solution. The program to decrease the amount of cocaine solution used was successful and will be expanded to other areas of the hospital.